Zn(OAc)2·2H2O: a versatile catalyst for the one-pot synthesis of propargylamines

Article abstract of DOI:10.1016/j.tetlet.2007.07.196

An inexpensive and readily available catalyst, Zn(OAc)₂·2H₂O is successfully evaluated for effective one-pot synthesis of propargylamines with moderate to excellent yields for most of the substrates screened, without the need of base, co-catalyst or additive in the presence of air.

Full text of DOI:10.1016/j.tetlet.2007.07.196

Tetrahedron Letters 48 (2007) 7184–7190
Zn(OAc)2Æ2H2O: a versatile catalyst for the one-pot
synthesis of propargylaminesI
Enugala Ramu,a Ravi Varala,b Nuvula Sreelathaa and Srinivas R. Adapaa,*
aIndian Institute of Chemical Technology, Hyderabad, India
bLab No: 202, Dept. of Quimica, Universidade Nova de Lisboa, (FCT/UNL), Caparica 2829-516, Portugal
Received 20 May 2007; revised 21 July 2007; accepted 30 July 2007
Available online 2 August 2007
Abstract—An inexpensive and readily available catalyst, Zn(OAc)2Æ2H2O is successfully evaluated for effective one-pot synthesis of
propargylamines with moderate to excellent yields for most of the substrates screened, without the need of base, co-catalyst or addi-
tive in the presence of air.
ꢀ 2007 Elsevier Ltd. All rights reserved.
Transition metal-catalyzed multi-component reactions
(MCR) are a powerful synthetic tool to access complex
structures from simple precursors via a one-pot proce-
dure and exhibit high atom economy and selectivity in
general.1 For example, improved syntheses of propar-
gylamines via the activation of a terminal alkyne C–H
bond using metal-catalyzed multi-component strategies
remain of continued interest to organic chemists in
terms of operational simplicity and cost effectiveness.
Being important building blocks and versatile synthons,
propargylamines are highly featured in organic synthe-
ses of many biologically active nitrogen containing com-
pounds such as conformationally restricted peptide
isosteres, oxotremorine analogues, allylamines, oxaz-
oles, pyrroles and b-lactams.2 Classical methods for
the preparation of propargylamines have usually
exploited the relatively high acidity of a terminal acetyl-
enic C–H bond to form alkynyl-metal reagents by reac-
tion with strong bases such as butyllithium,3a
organomagnesium compounds3b or LDA4 in a separate
step. Unfortunately, these reagents are required in stoi-
chiometric quantities, are highly moisture sensitive and
require strictly controlled reaction conditions.
to carbon–nitrogen double bonds either preformed (imi-
nes) or in one-pot (from aldehyde and amine) by
employing various transition metal catalysts such as
copper,5 silver,6 iridium,7 gold,8 zinc,9 zirconium10 and
rhenium11 for generation of metal acetylides under mild
reaction conditions for propargylamine synthesis.
Although several methods for construction of such units
have been reported,5–11 some required expensive Au,8
Ag,6 zirconium,10 iridium7 or rhenium11 as catalyst,
while some were limited to only one kind of aldehyde
(aromatic6 or aliphatic8), or an aromatic aldehyde and
primary amine in the presence of RuCl3 as a cocata-
lyst,5b or requirement of strictly anhydrous conditions.
The other systems are limited in the addition of propar-
gylamines to aldimines.7,9–11
To date, a truly efficient one-pot, three-component cou-
pling of an aldehyde, an alkyne and an amine (A3 cou-
pling) using zinc salts in a catalytic amount, without
any additive or base or the absence of inert conditions
has not been explored.9 The first zinc-catalyzed addition
of alkynes to a C@N electrophile was reported by Car-
riera et al. in which they treated alkynes with nitrones9a,c
(10 mol % Zn(OTf) , 25 mol % Hunig’s base in DCM)
¨
2
In recent years, enormous progress has been made in
expanding the scope of the direct addition of alkynes
or N-acyliminium ions9g (1.2 equiv Zn(OTf)2, 1.32 equiv
Et3N, 1.32 equiv TMPDA in toluene) at room tempera-
ture under strictly anhydrous conditions. Vallee et al.9b
employed substoichiometric amounts of Et2Zn
(0.2 equiv) for the addition of alkynes to nitrones in
the absence of any base under N2. In contrast, Jiang
et al.9f used ZnCl2 (1 mmol), Et3N (1.2 equiv) and
TMSCl (1.5 equiv) as activator for the addition of
Keywords: Three-component coupling; Zinc acetate; Propargylamines;
Catalysis.
q IICT Communication No.: 070109.
*
Corresponding author. Tel.: +91 40 27193169; fax: +91 40
27160921; e-mail: rvarala_iict@yahoo.co.in
0040-4039/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.07.196

E. Ramu et al. / Tetrahedron Letters 48 (2007) 7184–7190
7185
phenyl acetylene to imines at 60 ꢁC in toluene as solvent
comparable with the conversion of 98%, when Et3N was
used). The A3 coupled product was fully characterized
by IR, 1H/13C NMR and mass spectral analyses.
Zn(OAc)2Æ2H2O alone in toluene generally does not dis-
solve at ambient temperature. In preheated reflux tem-
peratures of toluene with catalyst also did not show
any homogeneous reaction mixture even after stirring
for several hours. Whereas, when the model reaction
was kept under preheated reflux conditions with the cat-
alyst (15 mol %) in toluene, it formed a homogeneous
mixture, thereby forming the adduct in the given time.
under an argon atmosphere. Kim et al.9e have employed
ZnBr (1 mmol) and Hunig’s base (1 mmol) in aceto-
¨
2
nitrile at 50–60 ꢁC for the addition of aryl acetylenes
to N-tosylimines to yield the corresponding propargylic
amines. Very recently, Bolm et al.9d reported a one-pot
synthesis of N-aryl propargylic amines using Me2Zn
(3.5 equiv) in anhydrous toluene without any additive
or base at room temperature for 2–4 days under an inert
atmosphere.
In the context of the above important contributions
utilizing zinc mediated chemistry9 for the synthesis of
propargylic amines, and being interested in exploring
novel synthetic strategies for C–C and C-hetero bond
formations,12 herein we describe Zn(OAc)2Æ2H2O as an
inexpensive, high yielding catalyst for the synthesis of
propargylamines without any activator or base under
aerobic conditions.
To the best of our knowledge, this is the first example of
a truly catalytic synthesis of propargylamines using zinc
salts. Surprisingly, a number of the other zinc salts sur-
veyed did not promote the reaction (entries 2–7, 10–12),
and instead gave unidentified by-products. As can be
seen from Table 1, entry 1 (ZnBr2) and entry 8
(Zn(OTf)2) gave the A2 coupled products in the presence
of Et3N and in the absence of base resulted in the
desired A3 coupled products in 10 h (92% and 94%,
respectively).
Initially, a series of zinc salts (15 mol % as standard)
were examined (Table 1) in toluene for the effective A3
coupling of benzaldehyde, piperidine and phenylacetyl-
ene in the presence and absence of Et3N. From these
studies, Zn(OAc)2Æ2H2O (entry 9) was found to be a
superior catalyst.
Interestingly, entry 13 (ZnO) gave the A2 coupled prod-
uct in the absence of base. When Zn(CN)2 (entry 14) was
employed as catalyst a mixture of A2 and A3 coupled
products was formed in a ratio of 3:1. No pinacol cou-
pled product was observed. In the absence of catalyst,
there was no reaction at all, even after stirring for 2 days
Despite the absence of Et3N, the corresponding A3 cou-
pled product was obtained with 96% conversion (almost
Table 1. Comparison of various Zn salts for the A3 coupling for the model reaction using benzaldehyde, piperidine and phenylacetylenea
OH
N
+
Ph
Ph
Ph
Ph
A2 Coupled product
A3 Coupled product
O
Zinc salt
Ph
H
+
+
OH
Toluene, reflux
Ph
N
H
H
Ph
Unidentified productsc
Ph
+
OH
Pinacol
Entry
Catalyst
Time (h)
Conversionsb (%)
With Et3N (1.2 equiv)
Without Et3N
1
ZnBr2
ZnCl2
Zn(NO3)2
Zn mont
Zn-Hydroxyapatite
Zn metal (granulated)
Zn dust
Zn(OTf)2
10
12
12
12
12
12
12
10
A2
0
0
0
0
0
0
A2
A3/92
0
0
0
2c
3c
4c
5c
6c
7c
8
0
0
0
A3/94
9
Zn(OAc)2Æ2H2O
7
A3/98
A3/96
10c
11c
12c
13
14
15
Zn(L-proline)2
ZnSO4
ZnCO3
ZnO
Zn(CN)2
—
12
12
12
12
12
48
0
0
0
0c
0
0
0
0
A2
A2(73):A3(27)
0
0
a Ratio of catalyst/benzaldehyde/piperidine/phenylacetylene = 0.15:1.0:1.3:1.5 and 3 mL of toluene, reflux.
b Conversions were determined by 1H NMR of the crude reaction mixture.
c Various unidentified products were observed.

7186
E. Ramu et al. / Tetrahedron Letters 48 (2007) 7184–7190
Table 3. Solvent studies under different parameters for the model
reaction catalyzed by Zn(OAc)2Æ2H2O
(entry 15). Having found the most effective catalyst
(Zn(OAc)2Æ2H2O in terms of yield, cost effectiveness
and reaction time), we address next optimization in
terms of loading and base screening (Table 2). In the
optimal process, 10 mol % of Zn(OAc)2Æ2H2O generated
the desired A3 product in 96% conversion (Table 2,
entry 7). Below 10 mol % of catalyst resulted in
decreased conversions (entries 8 and 9).
Entry
Solvent
Time (h)/
conversion (%)a
Time (h)/
conversion (%)a
rtb
Sonicationc
Reflux
1d
2d
3
MeOH
1,4-Dioxane
H2O
24/0
24/0
24/0
Gg
G
12/0
12/0
12/10
G
Use of a substoichiometric (20 mol %) amount of Et3N
as additive gave only a small increase in the yield (entry
2). Replacement of Et3N with other bases such as
DIPEA, DBU, DABCO, pyridine, Na2CO3, K2CO3,
Cs2CO3, CsOHÆH2O, NaOAc and K3PO4 (Table 2,
entries 10–19), had no influence on the process. When
DIPEA (entry 10) or DABCO (entry 12) were employed,
formation of the A2 coupled product was observed.
4
Toluene
24/0
0
07/96(92)f/(89)j
5
6d
7d
8
9d
10
11d
12
13
14
THF
DMF
24/0
24/0
24/0
24/0
24/0
24/0
24/0
24/0
24/0
24/0
G
G
G
G
G
G
G
G
G
G
10/ 92
12/0
12/0
12/Trace
12/0
12/89
12/0
12/0e
07/85, 80h
07/78,74i
CH3CN
DCM
DMSO
CHCl3
AcOH
Neat
PEG-600
[Bmim][BF4]
The screening of a range of solvents (10 mol % Zn-
(OAc)2Æ2H2O, no base, reflux) show that the solvent
had a strong effect (Table 3). From Table 3, we can see
that in all the solvents (entries 1–14), no desired product
was obtained at room temperature even after stirring for
24 h. The reactions performed in THF (entry 5) and
CHCl3 (entry 10) under reflux were successful, albeit,
with slightly lower yields compared to toluene (entry
4). When water was used as the solvent (entry 3), the
conversion was low (10%), whereas the other solvents
failed to give A3 product. Under solvent-free conditions,
heating the reaction mixture to 120 ꢁC did not lead to
the desired product.
a Conversions based on 1H NMR analysis.
b rt = Room temperature.
c Under sonication at 80 ꢁC [Elmasonic S 40H].
d Unidentified complex mixture.
e Reaction run at 120 ꢁC.
f Isolated yield in parentheses.
g G = Reaction not performed.
h Yield after 3rd recycle.
i Yield after 3rd recycle.
j Isolated yield in a 50 mmol scale reaction.
from the reaction mixture by the addition of ether and
the recovered PEG-600 was reused without any pre-
treatment, at least three times with only a slight decrease
in conversion (entry 13). The A3 coupling reaction in
[Bmim][BF4] gave a 78% conversion in 7 h. The recycl-
ability of [Bmim][BF4] in the A3 coupling reaction was
examined. It is noteworthy that the catalyst exhibited
comparable activity even after the third cycle as shown
in Table 3 (entry 14).
Next, we hoped to extend the range of solvents to also
polyethylene glycol and ionic liquids. Interestingly,
when we performed the reaction in PEG-600 at 120 ꢁC
for 7 h, we observed formation of a significant amount
of the desired product (85%). The product was extracted
Table 2. Optimization of the catalyst loading and base screening
Entry
Catalyst
loading
Base
Conversiona
(%)
Intrigued by these observations, we also performed the
reaction under ultrasonication in a preheated water bath
at 80 ꢁC for 30 min (entry 4), however no product for-
mation was observed. When acetic acid (Table 3, entry
11) was employed as solvent, there was no reaction.
1
2
3
4
5
6
15 mol %
10 mol %
1.0 equiv
0.5 equiv
30 mol %
15 mol %
Et3N(1.2 equiv)
Et3N(0.2 equiv)
No base
No base
No base
98
98
99
98
96
96
No base
In order to confirm whether reflux conditions were
needed for effective A3 coupling, we carried out several
parallel experiments. The reaction did not proceed at
temperatures of À78 ꢁC, 0 ꢁC, À5 ꢁC, 60 ꢁC and 90 ꢁC,
even after being stirred for 12 h.
7
10 mol %
No base
96
8
9
5 mol %
2 mol %
No base
No base
89
52
0
0
0
0
0
0
0
10b
11
12b
13
14
15
16
17
18
19
10 mol %
10 mol %
10 mol %
10 mol %
10 mol %
10 mol %
10 mol %
10 mol %
10 mol %
10 mol %
DIPEA(1.2 equiv)
DBU(1.2 equiv)
DABCO(1.2 equiv)
Pyridine(1.2 equiv)
Na2CO3(1.2 equiv)
K2CO3(1.2 equiv)
Cs2CO3(1.2 equiv)
CsOHH2O(1.2 equiv)
NaOAc(1.2 equiv)
K3PO4(1.2 equiv)
When the test reaction was conducted under inert condi-
tions using either argon or nitrogen, the yields were
comparable to those obtained under aerobic conditions.
To demonstrate the scope of this protocol, the model
reaction was performed on a 50 mmol scale (Table 3,
entry 4). The reaction was complete in 7 h affording
the corresponding product in 89% isolated yield.
0
0
0
a Determined by 1H NMR spectroscopy prior to chromatography.
b A2 coupling product.
After reaction establishing parameters for the model
reaction, we then proceeded to apply the catalytic

E. Ramu et al. / Tetrahedron Letters 48 (2007) 7184–7190
7187
Table 4. Zn(OAc)2Æ2H2O-catalyzed synthesis of propargylamines
Table 4 (continued)
EntryRef.
Product
Time (h) Yielda (%)
EntryRef.
Product
Time (h) Yielda (%)
15a X = CH2
25a X = O
3 X = S
4 X = NH
5 X = N–CH3
6 X = N–CH2Ph
7 X = N–Pyridyl
7
7
7
7
7
7
7
92
96
94
85
89
86
80
X
N
X
N
32 o-OH, X = CH2
33 m-OH, X = O
34 o-OH,
X = N–CH2Ph
35 m-OH,
9
9
9
76
72
69
Ph
Ph
9
89
HO
X = N–CH2Ph
X
N
X
N
86a X = CH2
95a X = O
8
8
88
86
36 X = CH2
37 X = O
7
7
93
91
Ph
Ph
OEt
H3C
X
X
N
N
38 X = CH2
395a X = O
12
12
56
72
105d X = CH2
115a X = O
12 X = N–CH3
13 X = N–CH2Ph
8
8
8
8
89
86
84
88
Ph
O2N
Ph
MeO
X
N
X
N
40 X = CH2
41 X = O
12
12
88
93
Ph
CN
MeO
MeO
14 X = CH2
15 X = O
8
8
86
90
X
Ph
428b X = CH2
43 X = O
12
12
85
88
N
OMe
X
N
Ph
F3C
445a R = H
45 R = p-CH3
46 R = p-OCH3
47 R = 3,4,5-
tri-OMe
48 R = p-Cl
49 R = p-F
50 R = p-Br
51 R = p-CF3
52 R = o-OH
53 Naphthyl
7
7
7
7
92
95
98
88
16 X = CH2
17 X = O
8
8
8
85
78
82
Ph
18 X = N–CH2Ph
Me2N
N
X
N
7
7
7
7
7
7
96
98
88
82
85
90
R
Ph
19 X = CH2
20 X = O
7
7
96
98
Ph
F
X
N
545a
8
92
215d X = CH2
225a X = O
7
98
N
Ph
Ph
7
7
96
89
Cl
X
23 X = N–CH2Ph
555d X = CH2
565a X = O
10
12
89
94
N
X
N
Ph
245d X = CH2
255a X = O
26 X = N–CH3
27 X = N–CH2Ph
10
14
14
14
96
88
85
84
X
Ph
Br
N
57 X = CH2
585a X = O
12
12
84
87
Ph
Ph
O
S
X
N
X
N
28 X = CH2
295a X = O
7
7
94
92
59 X = CH2
605d X = O
12
12
92
96
Ph
F
X
N
X
N
61 X = CH2
62 X = O
24
24
0
0
30 X = CH2
315a X = O
7
7
92
98
Ph
N
Ph
(continued on next page)
Cl

7188
E. Ramu et al. / Tetrahedron Letters 48 (2007) 7184–7190
Table 4 (continued)
Table 4 (continued)
EntryRef.
Product
Time (h) Yielda (%)
EntryRef.
Product
Time (h) Yielda (%)
X
X
N
63 X = CH2
64 X = O
12
12
82
90
N
97 X = CH2
985a X = O
8
9
86
82
TMS
Ph
X
N
99 X = CH2;
R = H
100 X = O;
R = H
101 X = CH2;
R = OH
8
8
8
90
88
84
X
N
65 X = CH2
66 X = O
12
12
62
65
Ph
OH
67 X = CH2
685a X = O
69 X = S
70 X = NH
71 X = N–CH3
72 X = NCH2Ph
73 X = N,N-
Diisopropyl
7
7
7
7
7
7
7
98
99
95
92
89
86
98
R
N
X
N
102
7
92
Ph
CH3
X
N
1035d n = 4;
X = CH2
1045a n = 4;
X = O
105 n = 7;
X = O
106 n = 7;
X = CH2
107 n = 5;
X = CH2
108 n = 5;
X = O
7
7
7
7
7
7
89
90
78
85
94
95
74 X = CH2
75 X = O
76 X = N–CH3
7
7
7
95
98
92
X
N
Ph
X
N
CH3
775d X = CH2
78 X = O
8
8
95
92
n
Ph
X
N
79 X = CH2
80 X = O
8
8
84
82
a Isolated yields.
Ph
X
N
81 X = CH2
82 X = O
8
8
88
82
system (10 mol %, toluene under reflux) for the reaction
of various secondary amines, aldehydes and phenylacet-
ylene as shown in Table 4 (See Supplementary data).13 A
wide range of structurally diverse functionalized pipera-
zines tolerated the reaction conditions (entries 1–7). The
electronic nature of the substituents on the aryl alde-
hydes had a pronounced effect on the overall efficiency
of the process.
Ph
83 R = n-butyl
84 R = n-pentyl
85 R = n-heptyl
86 R = n-propyl
87 R = i-butyl
7
7
7
7
7
7
98
92
95
89
91
98
N
R
Ph
88 R = cyclohexyl
X
N
Substrates bearing electron-rich substitutents (entries 8–
37) all gave good conversions, whereas aryl aldehydes
possessing electron-withdrawing groups (entries 38–43)
required longer times. Halogenated substituted alde-
hydes (entries 19–31) gave the corresponding A3 coupled
products in almost quantitative yields.
896a X = CH2
905a X = O
7
7
99
95
Ph
HN
91
12
68
2- and 3-Hydroxy benzaldehydes also furnished the cor-
responding A3 coupled products under the optimized
conditions, whereas earlier literature reported failures
(entries 32–35). 2-Naphthaldehyde also produced corre-
sponding addition products in good yields (entries 53,
55–56). Heteroaromatic aldehydes such as furfur-
aldehyde and thiophene 2-carboxaldehyde gave the
corresponding A3 products in good yields (entries 57–
60). Interestingly, pyridine 2-carboxaldehyde did not
give the addition product (entries 61–62). We have also
successfully employed different aliphatic aldehydes in
Ph
92 R = R1 = allyl
93 R = CH2Ph;
R1 = H
12
12
0
0
R1
R
N
94 R = R1 =
CH2Ph
12
0
Ph
95 R = R1 = CH3
96 R = H; R1 = Ph
12
12
0
0

E. Ramu et al. / Tetrahedron Letters 48 (2007) 7184–7190
7189
H C
AcO Zn
Ph
Supplementary data
HC
Ph
Zn(OAc)2 2H2O
OAc
2H2O
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.
2007.07.196.
Ph
OAc
H
C
N
C
H
AcO Zn
2H2O
C
R
C
Ph
HOAc
Zn
C
2H2O
AcO
Ph
H
References and notes
H
C
N
1. Multicomponent reactions; Zhu, J., Bienayme, H., Eds.;
Wiley: Weinheim, 2005.
2. (a) Zani, L.; Bolm, C. Chem. Commun. 2006, 4263, and
references cited therein; (b) Wei, C.; Li, Z.; Li, C.-J.
Synlett 2004, 1472.
3. (a) Wakefield, B. J. Organolithium Methods in Organic
Synthesis; Academic Press: London, 1988; Chapter 3, pp
32; (b) Wakefield, B. J. Organomagnesium Methods in
Organic Synthesis; Academic Press: London, 1995; Chap-
ter 3, pp 46.
R
+
AcO Zn
C
Ph
N
2H2O
C
R
HOAc
O
C
+
R
H
N
H
Scheme 1.
4. (a) Harada, T.; Fujiwara, T.; Iwazaki, K.; Oku, A. Org.
Lett. 2000, 2, 1855; (b) Rosas, N.; Sharma, P.; Alvarez, C.;
Gomez, E.; Gutierrez, Y.; Mendez, M.; Toscano, R. A.;
Maldonado, L. A. Tetrahedron Lett. 2003, 44, 8019; (c)
Ding, C.-H.; Chen, D.-D.; Luo, Z.-B.; Dai, L.-X.; Hou,
X.-L. Synlett 2006, 1272.
5. Copper: (a) Shi, L.; Tu, Y. Q.; Wang, M.; Zhang, F. M.;
Fan, C. A. Org. Lett. 2004, 6, 1001; (b) Li, C.-J.; Wei, C.
Chem. Commun. 2002, 268; (c) Wei, C.; Li, C.-J. J. Am.
Chem. Soc. 2002, 124, 5638; (d) Park, S. B.; Alper, H.
Chem. Commun. 2005, 1315; (e) Black, D. A.; Arndtsen, B.
A. Tetrahedron 2005, 61, 11317; (f) Taylor, A. M.;
Schreiber, S. L. Org. Lett. 2006, 8, 143; (g) Gommermann,
N.; Knochel, P. Chem. Commun. 2004, 2324; (h) Gom-
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Angew. Chem., Int. Ed. 2003, 42, 5763; (i) Gommermann,
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J. Org. Chem. 2006, 71, 2064.
our catalytic system (entries 67–90). Trimerization of
aldehydes was never observed using Zn(OAc)2Æ2H2O
as catalyst, while it was a major limitation of the A3
coupling using Au8 and Cu5. Diisopropylamine and
cyclohexylamine were also tolerated (entries 54, 73 and
91) under the present conditions. Diallylamine, benzyl-
amine, dibenzylamine, dimethylamine and aniline
(entries 92–96) were not tolerated under the optimized
conditions. Other acetylenic substrates such as tri-
methylsilyl acetylene, propargyl alcohol and simple
aliphatic alkynes also underwent the reaction (entries
97–108). This indicates that the Zn(OAc)2Æ2H2O is also
compatible with both aromatic and aliphatic alkynes
as well.
A tentative mechanism is proposed involving the Lewis
acid (Zn(II)) assisted proton transfer with the alkyne to
form the corresponding zinc acetylide (Scheme 1). The
zinc acetylide intermediate thus generated reacts with
the iminium ion generated in situ from an aldehyde
and secondary amine to give the corresponding propar-
gylamine and regenerate the Zn(II) catalyst for further
reaction.
6. Silver: (a) Wei, C.; Li, Z.; Li, C.-J. Org. Lett. 2003, 5, 4473;
(b) Ji, J.-X.; Au-Yeung, T. T. L.; Wu, J.; Yip, C. W.;
Chan, A. S. C. Adv. Synth. Catal. 2004, 346, 42; (c) Yan,
W.; Wang, R.; Xu, Z.; Xu, J.; Lin, Li.; Shen, Z.; Zhou, Y.
J. Mol. Catal. A: Chem. 2006, 255, 81; (d) Li, Z.; Wei, C.;
Chen, L.; Varma, R. S.; Li, C.-J. Tetrahedron Lett. 2004,
45, 2443.
7. Iridium: Fischer, C.; Carreira, E. M. Org. Lett. 2001, 3,
4319.
In conclusion, we have successfully developed an effi-
cient protocol using Zn(OAc)2Æ2H2O as catalyst for the
one-pot synthesis of diverse propargylamines for the
first time in moderate to excellent yields. Notable fea-
tures of the protocol are: clean and simple reaction con-
ditions; use of a readily available and inexpensive
catalyst; tolerability of various functional groups and
aerobic conditions. We believe that this protocol will
be a valuable addition to modern synthetic methodolo-
gies for one-pot syntheses of propargylamines. An
asymmetric version of the same transformation is cur-
rently under investigation in our lab.
8. Gold: gold saline complex: (a) Lo, V. K.-Y.; Liu, Y.;
Wong, M.-K.; Che, C.-M. Org. Lett. 2006, 8, 1529; (b)
Wei, C.; Li, C.-J. J. Am. Chem. Soc. 2003, 125, 9584.
9. Zn: (a) Frantz, D. E.; Fassler, R.; Carreira, E. M. J. Am.
Chem. Soc. 1999, 121, 11245; (b) Pinet, S.; Pandya, S. U.;
Chavant, P. Y.; Ayling, A.; Vallee, Y. Org. Lett. 2002, 4,
1463; (c) Zani, L.; Alesi, S.; Cozzi, P. G.; Bolm, C. J. Org.
Chem. 2006, 71, 1558; (d) Lee, K.-Y.; Lee, C.-G.; Na, J.-
E.; Kim, J.-N. Tetrahedron Lett. 2005, 46, 69; (e) Jiang, B.;
Si, Y.-G. Tetrahedron Lett. 2003, 44, 6767; (f) Fischer, C.;
Carreira, E. M. Org. Lett. 2004, 6, 1497; (g) Jiang, B.; Si,
Y.-G. Angew. Chem., Int. Ed. 2004, 43, 216.
10. Zr: (a) Traverse, J. F.; Hoveyda, A. H.; Snapper, M. L.
Org. Lett. 2003, 5, 3273; (b) Akullian, L. C.; Snapper, M.
L.; Hoveyda, A. H. Angew. Chem., Int. Ed. 2003, 42, 4244.
11. Re: Kuninobu, Y.; Inoue, Y.; Takai, K. Chem. Lett. 2006,
35, 1376.
Acknowledgements
12. (a) Varala, R.; Sreelatha, N.; Adapa, S. R. J. Org. Chem.
2006, 71, 8283; (b) Varala, R.; Nasreen, A.; Ramu, E.;
Adapa, S. R. Tetrahedron Lett. 2007, 48, 69; (c) Varala,
R.; Sreelatha, N.; Adapa, S. R. Synlett 2006, 1549, and
R.V. and R.E. sincerely thank Dr. J. S. Yadav, Director,
IICT and CSIR, India, for providing necessary facilities
and funding.

7190
E. Ramu et al. / Tetrahedron Letters 48 (2007) 7184–7190
1152, 757, 693 cmÀ1
references cited therein; (d) Varala, R.; Ramu, E.; Adapa,
S. R. Synthesis 2006, 22, 3825.
13. General procedure. stirred solution of alkyne
:
1H NMR (300 MHz, CDCl3):
d = 1.38–1.50 (m, 2H), 1.52–1.66 (m, 4H), 2.52–2.62 (m,
4H), 4.80 (s, 1H), 7.26–7.38 (m, 6H), 7.48–7.54 (m, 2H),
7.60–7.64 (m, 2H); 13C NMR (75 MHz, CDCl3): d = 24.3,
26.1, 50.6, 62.3, 86.0, 87.8, 123.2, 127.3, 127.9, 128.2,
128.4, 131.7, 138.5; MS (EI) m/z = 275, 274, 198, 191,
115.Table 4, entry 89: IR (Neat): 3054, 2930, 2852, 2751,
1598, 1489, 1443, 1318, 1156, 1103, 890, 755, 691; 1H
NMR (300 MHz, CDCl3): d = 0.88–1.10 (m, 2H), 1.11–
1.34 (m, 3H), 1.36–1.49 (m, 2H), 1.49–1.69 (m, 6H),
1.71–1.82 (m, 2H), 1.98–2.15 (m, 2H), 2.32–2.44 (m, 2H),
2.58–2.66 (m, 2H), 3.11 (d, J = 9.8 Hz, 1H), 7.25–7.31
(m, 3H), 7.41–7.45 (m, 2H); 13C NMR (75 MHz, CDCl3):
d = 24.9, 26.3, 26.5, 27.0, 30.6, 31.6, 39.8, 64.6, 86.3, 88.0,
124.0, 127.8, 128.4, 132.0; MS (FAB) m/z = 280 (M++H),
241, 198, 141, 115.
A
(1.5 mmol), Zn(OAc)2Æ2H2O (0.1 mmol), aldehyde
(1.0 mmol) and amine (1.3 mmol) in toluene (3 mL) was
taken in a round-bottomed flask and inserted into a
preheated oil bath (120 ꢁC bath temperature). After
completion of the reaction (as monitored by TLC), the
reaction mixture was diluted with aq NH4Cl (2 · 5 mL)
and stirred for 5 min. The aqueous layers were extracted
with diethyl ether (2 · 10 mL), dried over Na2SO4 and
concentrated to give the crude product which was further
purified by column chromatography on silica gel (ethyl
acetate/hexane = 1:6) to afford the corresponding pure
propargylamine. Representative examples. Table 4, entry
1: IR (KBr): 3055, 2930, 2747, 1598, 1486, 1443, 1318,